Low crossing profile delivery catheter for cardiovascular prosthetic implant

ABSTRACT

A delivery catheter and a method for deploying a cardiovascular prosthetic implant using a minimally invasive procedure are disclosed. The delivery catheter comprises an elongate, flexible catheter body having a proximal end and a distal end, wherein the distal end has an outer diameter of 18 French or less, a cardiovascular prosthetic implant at the distal end of the catheter body, wherein the cardiovascular prosthetic implant comprises an inflatable cuff and a tissue valve coupled to the inflatable cuff, and at least one link between the catheter body and the cardiovascular prosthetic implant.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/110,780, filed on May 18, 2011, which claims the priority benefit toU.S. Provisional No. 61/346,390 filed May 19, 2010 and U.S. ProvisionalNo. 61/411,862 filed Nov. 9, 2010, the entireties of which are herebyincorporated by reference herein.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to medical methods and devices, and, inparticular, to a low crossing profile delivery catheter forpercutaneously implanting a cardiovascular implant having aformed-in-place support structure.

Description of the Related Art

According to recent estimates, more than 79,000 patients are diagnosedwith aortic and mitral valve disease in U.S. hospitals each year. Morethan 49,000 mitral valve or aortic valve replacement procedures areperformed annually in the U.S., along with a significant number of heartvalve repair procedures.

The circulatory system is a closed loop bed of arterial and venousvessels supplying oxygen and nutrients to the body extremities throughcapillary beds. The driver of the system is the heart providing correctpressures to the circulatory system and regulating flow volumes as thebody demands. Deoxygenated blood enters heart first through the rightatrium and is allowed to the right ventricle through the tricuspidvalve. Once in the right ventricle, the heart delivers this bloodthrough the pulmonary valve and to the lungs for a gaseous exchange ofoxygen. The circulatory pressures carry this blood back to the heart viathe pulmonary veins and into the left atrium. Filling of the left atriumoccurs as the mitral valve opens allowing blood to be drawn into theleft ventricle for expulsion through the aortic valve and on to the bodyextremities. When the heart fails to continuously produce normal flowand pressures, a disease commonly referred to as heart failure occurs.

Heart failure simply defined is the inability for the heart to produceoutput sufficient to demand. Mechanical complications of heart failureinclude free-wall rupture, septal-rupture, papillary rupture ordysfunction aortic insufficiency and tamponade. Mitral, aortic orpulmonary valve disorders lead to a host of other conditions andcomplications exacerbating heart failure further. Other disordersinclude coronary disease, hypertension, and a diverse group of musclediseases referred to as cardiomyopothies. Because of this syndromeestablishes a number of cycles, heart failure begets more heart failure.

Heart failure as defined by the New York Heart Association in afunctional classification.

-   -   I. Patients with cardiac disease but without resulting        limitations of physical activity. Ordinary physical activity        does not cause undue fatigue, palpitation, dyspnea, or anginal        pain.    -   II. Patient with cardiac disease resulting in slight limitation        of physical activity. These patients are comfortable at rest.        Ordinary physical activity results in fatigue, palpitation,        dyspnea, or anginal pain.    -   III. Patients with cardiac disease resulting in marked        limitation of physical activity. These patients are comfortable        at rest. Less than ordinary physical activity causes fatigue        palpitation, dyspnea, or anginal pain.    -   IV. Patients with cardiac disease resulting in inability to        carry on any physical activity without discomfort. Symptoms of        cardiac insuffiency or of the anginal syndrome may be present        even at rest. If any physical activity is undertaken, discomfort        is increased.

There are many styles of mechanical valves that utilize both polymer andmetallic materials. These include single leaflet, double leaflet, balland cage style, slit-type and emulated polymer tricuspid valves. Thoughmany forms of valves exist, the function of the valve is to control flowthrough a conduit or chamber. Each style will be best suited to theapplication or location in the body it was designed for.

Bioprosthetic heart valves comprise valve leaflets formed of flexiblebiological material. Bioprosthetic valves or components from humandonors are referred to as homografts and xenografts are from non-humananimal donors. These valves as a group are known as tissue valves. Thistissue may include donor valve leaflets or other biological materialssuch as bovine pericardium. The leaflets are sewn into place and to eachother to create a new valve structure. This structure may be attached toa second structure such as a stent or cage or other prosthesis forimplantation to the body conduit.

Implantation of valves into the body has been accomplished by a surgicalprocedure and has been attempted via percutaneous method such as acatheterization or delivery mechanism utilizing the vasculaturepathways. Surgical implantation of valves to replace or repair existingvalves structures include the four major heart valves (tricuspid,pulmonary, mitral, aortic) and some venous valves in the lowerextremities for the treatment of chronic venous insufficiency.Implantation includes the sewing of a new valve to the existing tissuestructure for securement. Access to these sites generally include athoracotomy or a sternotomy for the patient and include a great deal ofrecovery time. An open-heart procedure can include placing the patienton heart bypass to continue blood flow to vital organs such as the brainduring the surgery. The bypass pump will continue to oxygenate and pumpblood to the body's extremities while the heart is stopped and the valveis replaced. The valve may replace in whole or repair defects in thepatient's current native valve. The device may be implanted in a conduitor other structure such as the heart proper or supporting tissuesurrounding the heart. Attachments methods may include suturing, hooksor barbs, interference mechanical methods or an adhesion median betweenthe implant and tissue.

Although valve repair and replacement can successfully treat manypatients with valvular insufficiency, techniques currently in use areattended by significant morbidity and mortality. Most valve repair andreplacement procedures require a thoracotomy, usually in the form of amedian sternotomy, to gain access into the patient's thoracic cavity. Asaw or other cutting instrument is used to cut the sternumlongitudinally, allowing the two opposing halves of the anterior orventral portion of the rib cage to be spread apart. A large opening intothe thoracic cavity is thus created, through which the surgical team maydirectly visualize and operate upon the heart and other thoraciccontents. Alternatively, a thoracotomy may be performed on a lateralside of the chest, wherein a large incision is made generally parallelto the ribs, and the ribs are spread apart and/or removed in the regionof the incision to create a large enough opening to facilitate thesurgery.

Surgical intervention within the heart generally requires isolation ofthe heart and coronary blood vessels from the remainder of the arterialsystem, and arrest of cardiac function. Usually, the heart is isolatedfrom the arterial system by introducing an external aortic cross-clampthrough a sternotomy and applying it to the aorta to occlude the aorticlumen between the brachiocephalic artery and the coronary ostia.Cardioplegic fluid is then injected into the coronary arteries, eitherdirectly into the coronary ostia or through a puncture in the ascendingaorta, to arrest cardiac function. The patient is placed onextracorporeal cardiopulmonary bypass to maintain peripheral circulationof oxygenated blood.

Since surgical techniques are highly invasive and in the instance of aheart valve, the patient must be put on bypass during the operation, theneed for a less invasive method of heart valve replacement has long beenrecognized. At least as early as 1972, the basic concept of suturing atissue aortic valve to an expandable cylindrical “fixation sleeve” orstent was disclosed. See U.S. Pat. No. 3,657,744 to Ersek. Other earlyefforts were disclosed in U.S. Pat. No. 3,671,979 to Moulopoulos andU.S. Pat. No. 4,056,854 to Boretos, relating to prosthetic valvescarried by an expandable valve support delivered via catheter for remoteplacement. More recent iterations of the same basic concept weredisclosed, for example, in patents such as U.S. Pat. Nos. 5,411,552,5,957,949, 6,168,614, and 6,582,462 to Anderson, et al., which relategenerally to tissue valves carried by expandable metallic stent supportstructures which are crimped to a delivery balloon for later expansionat the implantation site.

In each of the foregoing systems, the tissue or artificial valve isfirst attached to a preassembled, complete support structure (some formof a stent) and then translumenally advanced along with the supportstructure to an implantation site. The support structure is thenforceably enlarged or allowed to self expand without any change in itsrigidity or composition, thereby securing the valve at the site.

Despite the many years of effort, and enormous investment ofentrepreneurial talent and money, no stent based heart valve system hasyet received regulatory approval, and a variety of difficulties remain.For example, stent based systems have a fixed rigidity even in thecollapsed configuration, and have inherent difficulties relating topartial deployment, temporary deployment, removal and navigation.

Thus, a need remains for improvements over the basic concept of a stentbased prosthetic valve. As disclosed herein a variety of significantadvantages may be achieved by eliminating the stent and advancing thevalve to the site without a support structure. Only later, the supportstructure is created in situ such as by inflating one or more inflatablechambers to impart rigidity to an otherwise highly flexible andfunctionless subcomponent.

SUMMARY OF THE INVENTION

One aspect of the present invention comprises a delivery catheter fordeploying a cardiovascular prosthetic implant using a minimally invasiveprocedure. The delivery catheter comprises an elongate, flexiblecatheter body having a proximal end and a distal end. The distal portionof the catheter has an outer diameter of 18 French or less. Acardiovascular prosthetic implant is positioned at the distal end of thecatheter body. The cardiovascular prosthetic implant comprises aninflatable cuff and a tissue valve having a thickness of at least about0.011 inches coupled to the inflatable cuff. At least one link isprovided between the catheter body and the cardiovascular prostheticimplant

Another aspect of the present invention comprises a method of deployinga cardiovascular prosthetic implant. The method includes translumenallyadvancing a catheter having a distal portion with a diameter of 18French and carrying a cardiovascular prosthetic implant with a tissuevalve having a thickness of at least about 0.011 inches to a positionproximate a native valve of a patient. The cardiovascular prostheticimplant comprises an inflatable cuff, a tissue valve coupled to theinflatable cuff. The inflatable cuff is inflated fully with a hardenableinflation media. The catheter is removed from the patient, leaving thehardenable inflation media in the cardiovascular prosthetic implantwithin the patient.

Another aspect of the present invention comprises a delivery catheterfor deploying a cardiovascular prosthetic implant using a minimallyinvasive procedure. The delivery catheter comprises an elongate,flexible catheter body having a proximal end and a distal end, whereinthe distal end has an outer diameter of 18 French or less. Acardiovascular prosthetic implant is positioned at the distal end of thecatheter body. The cardiovascular prosthetic implant comprises a supportstructure and a tissue valve having a thickness of at least about 0.011inches coupled to the support structure

Another aspect of the present invention comprises a method of deployinga cardiovascular prosthetic implant. The method comprises translumenallyadvancing a catheter having a distal portion with a diameter of 18French and carrying a cardiovascular prosthetic implant with a tissuevalve having a thickness of at least about 0.011 inches to a positionproximate a native valve of a patient. The cardiovascular prostheticimplant is deployed within the patient and the catheter is removed fromthe patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional schematic view of a heart and its majorblood vessels.

FIG. 2A is a partial cut-away view a left ventricle and aortic with anprosthetic aortic valve implant according to one embodiment of thepresent invention positioned therein.

FIG. 2B is a side view of the implant of FIG. 2A positioned across anative aortic valve.

FIG. 3A is a front perspective view of the implant of FIG. 2B.

FIG. 3B is a front perspective view of an inflatable support structureof the implant of FIG. 3A.

FIG. 3C is a cross-sectional side view of the implant of FIG. 3A.

FIG. 3D is an enlarged cross-sectional view of an upper portion of FIG.3C.

FIG. 4 is a cross-sectional view of the connection port and theinflation valve in the implant of FIG. 3B.

FIG. 5A is a side perspective view of a deployment catheter withretracted implant.

FIG. 5B is a side perspective view of the deployment catheter of FIG. 5Awith the implant outside of the outer sheath jacket.

FIG. 5C is a side perspective view of the position-and-fill lumen (PFL),which is a component of the deployment catheter of FIGS. 5A and 5B.

FIG. 6 is a cross-sectional view taken through line A-A of FIG. 5B.

FIG. 7 is a side perspective view of a loading tool base.

FIGS. 8A-C illustrate time sequence steps of partially deploying andpositioning an artificial valve implant.

FIGS. 9A-E illustrates time sequence steps of deploying, testing andrepositioning an artificial valve implant.

FIGS. 10A-C illustrates time sequence steps of deploying and withdrawingan artificial valve implant.

FIG. 11 is a side perspective view of an embodiment of recovery catheterfor retrieving the implant in the patient.

FIG. 12 is a side perspective view of a method of compressing theimplant of FIGS. 3A-B.

DETAILED DESCRIPTION OF THE EMBODIMENTS

FIG. 1 is a schematic cross-sectional illustration of the anatomicalstructure and major blood vessels of a heart 10. Deoxygenated blood isdelivered to the right atrium 12 of the heart 10 by the superior andinferior vena cava 14, 16. Blood in the right atrium 12 is allowed intothe right ventricle 18 through the tricuspid valve 20. Once in the rightventricle 18, the heart 10 delivers this blood through the pulmonaryvalve 22 to the pulmonary arteries 24 and to the lungs for a gaseousexchange of oxygen. The circulatory pressures carry this blood back tothe heart via the pulmonary veins 26 and into the left atrium 28.Filling of the left atrium 28 occurs as the mitral valve 30 opensallowing blood to be drawn into the left ventricle 32 for expulsionthrough the aortic valve 34 and on to the body extremities through theaorta 36. When the heart 10 fails to continuously produce normal flowand pressures, a disease commonly referred to as heart failure occurs.

One cause of heart failure is failure or malfunction of one or more ofthe valves of the heart 10. For example, the aortic valve 34 canmalfunction for several reasons. For example, the aortic valve 34 may beabnormal from birth (e.g., bicuspid, calcification, congenital aorticvalve disease), or it could become diseased with age (e.g., acquiredaortic valve disease). In such situations, it can be desirable toreplace the abnormal or diseased valve 34.

FIG. 2 is a schematic illustration of the left ventricle 32, whichdelivers blood to the aorta 36 through the aortic valve 34. The aorta 36comprises (i) the ascending aorta 38, which arises from the leftventricle 32 of the heart 10, (ii) the aortic arch 10, which arches fromthe ascending aorta 38 and (iii) the descending aorta 42 which descendsfrom the aortic arch 40 towards the abdominal aorta (not shown). Alsoshown are the principal branches of the aorta 14, which include theinnomate artery 44 that immediately divides into the right carotidartery (not shown) and the right subclavian artery (not shown), the leftcarotid 46 and the subclavian artery 48.

Inflatable Prosthetic Aortic Valve Implant

With continued reference to FIG. 2A, a cardiovascular prosthetic implant800 in accordance with an embodiment of the present invention is shownspanning the native abnormal or diseased aortic valve 34. The implant800 and various modified embodiments thereof will be described in detailbelow. As will be explained in more detail below, the implant 800 ispreferably delivered minimally invasively using an intravasculardelivery catheter 900 or trans apical approach with a trocar.

In the description below, the present invention will be describedprimarily in the context of replacing or repairing an abnormal ordiseased aortic valve 34. However, various features and aspects ofmethods and structures disclosed herein are applicable to replacing orrepairing the mitral 30, pulmonary 22 and/or tricuspid 20 valves of theheart 10 as those of skill in the art will appreciate in light of thedisclosure herein. In addition, those of skill in the art will alsorecognize that various features and aspects of the methods andstructures disclosed herein can be used in other parts of the body thatinclude valves or can benefit from the addition of a valve, such as, forexample, the esophagus, stomach, ureter and/or vesice, biliary ducts,the lymphatic system and in the intestines.

In addition, various components of the implant and its delivery systemwill be described with reference to coordinate system comprising“distal” and “proximal” directions. In this application, distal andproximal directions refer to the deployment system 900, which is used todeliver the implant 800 and advanced through the aorta 36 in a directionopposite to the normal direction of blood through the aorta 36. Thus, ingeneral, distal means closer to the heart while proximal means furtherfrom the heart with respect to the circulatory system.

In some embodiments, the implant 800 may be a prosthetic aortic valveimplant. With reference to FIG. 2B in the illustrated embodiment, theimplant 800 has a shape that can be viewed as a tubular member orhyperboloid shape where a waist 805 excludes the native valve 34 orvessel and proximally the proximal end 803 forms a hoop or ring to sealblood flow from re-entering the left ventricle 32. Distally, the distalend 804 also forms a hoop or ring to seal blood from forward flowthrough the outflow track. Between the two ends 803 and 804, the valve104 is mounted to the cuff or body 802 such that when inflated theimplant 800 excludes the native valve 34 or extends over the formerlocation of the native valve 34 and replaces its function. The distalend 804 should have an appropriate size and shape so that it does notinterfere with the proper function of the mitral valve, but stillsecures the valve adequately. For example, there may be a notch, recessor cut out in the distal end 804 of the device to prevent mitral valveinterference. The proximal end 803 is designed to sit in the aorticroot. It is preferably shaped in such a way that it maintains goodapposition with the wall of the aortic root. This prevents the devicefrom migrating back into the ventricle 32. In some embodiments, theimplant 800 is configured such that it does not extend so high that itinterferes with the coronary arteries.

Any number of additional inflatable rings or struts may be disposedbetween the proximal end 803 and distal end 804. The distal end 804 ofthe implant 800 is preferably positioned within the left ventricle 34and can utilize the aortic root for axial stabilization as it may have alarger diameter than the aortic lumen. This may lessen the need forhooks, barbs or an interference fit to the vessel wall. Since theimplant 800 may be placed without the aid of a dilatation balloon forradial expansion, the aortic valve 34 and vessel may not have anyduration of obstruction and would provide the patient with more comfortand the physician more time to properly place the device accurately.Since the implant 800 is not utilizing a support member with a singleplacement option as a plastically deformable or shaped memory metalstent does, the implant 800 may be movable and or removable if desired.This could be performed multiple times until the implant 800 ispermanently disconnected from the delivery catheter 900 as will beexplained in more detail below. In addition, the implant 800 can includefeatures, which allow the implant 800 to be tested for proper function,sealing and sizing, before the catheter 900 is disconnected.

With reference to FIG. 3A, the implant 800 of the illustrated embodimentgenerally comprises an inflatable cuff or body 802, which is configuredto support a valve 104 (see FIG. 2A) that is coupled to the cuff 802. Insome embodiments, the valve 104 is a tissue valve. In some embodiments,the tissue valve has a thickness equal to or greater than about 0.011inches. In another embodiment, the tissue valve has a thickness equal toor greater than about 0.018 inches. As will be explained in more detailbelow, the valve 104 is configured to move in response to thehemodynamic movement of the blood pumped by the heart 10 between an“open” configuration where blood can throw the implant 800 in a firstdirection (labeled A in FIG. 2B) and a “closed” configuration wherebyblood is prevented from back flowing through the valve 104 in a seconddirection B (labeled B in FIG. 2B).

In the illustrated embodiment, the cuff 802 comprises a thin flexibletubular material such as a flexible fabric or thin membrane with littledimensional integrity. As will be explained in more detail below, thecuff 802 can be changed preferably, in situ, to a support structure towhich other components (e.g., the valve 104) of the implant 800 can besecured and where tissue ingrowth can occur. Uninflated, the cuff 802 ispreferably incapable of providing support. In one embodiment, the cuff802 comprises Dacron, PTFE, ePTFE, TFE or polyester fabric as seen inconventional devices such as surgical stented or stent less valves andannuloplasty rings. The fabric thickness may range from about 0.002inches to about 0.020 inches depending upon material selection andweave. Weave density may also be adjusted from a very tight weave toprevent blood from penetrating through the fabric to a looser weave toallow tissue to grow and surround the fabric completely. In preferredembodiments, the fabric may have a linear mass density about 20 denieror lower.

With reference to FIGS. 3B-3D, in the illustrated embodiment, theimplant 800 includes an inflatable structure 813 that is formed by oneor more inflation channels 808. The inflatable channels 808 are formedby a pair of distinct balloon rings or toroids (807 a and 807 b) andstruts 806. In the illustrated embodiment, the implant 800 comprises aproximal toroid 807 a at the proximal end 803 of the cuff 802 and adistal toroid 807 b at the distal end 804 of the cuff 802. The toroids807 can be secured to the cuff 802 in any of a variety of manners. Withreference to FIGS. 3C and 3D, in the illustrated embodiment, the toroids807 are secured within folds 801 formed at the proximal end 803 and thedistal end 804 of the cuff 802. The folds 801, in turn, are secured bysutures or stitches 812. When inflated, the implant 800 is supported inpart by series of struts 806 surrounding the cuff 802. In someembodiments, the struts 806 are configured so that the portions on thecuff run substantially perpendicular to the toroids. In someembodiments, the struts are sewn onto the cuff 802 or are enclosed inlumens made from the cuff material and swan onto the cuff 802. Thetoroids 807 and the struts 806 together form one or more inflatablechannels 808 that can be inflated by air, liquid or inflation media.

With reference to FIG. 3B, the inflation channels are configured so thatthe cross-sectional profile of the implant 800 is reduced when it iscompressed or in the retracted state. The inflation channels 808 arearranged in a step-function pattern. The inflation channels 808 havethree connection ports 809 for coupling to the delivery catheter 900 viaposition and fill lumen tubing (PFL) tubing 916 (see FIGS. 5A-5C). Insome embodiments, at least two of the connection ports 809 also functionas inflation ports, and inflation media, air or liquid can be introducedinto the inflation channel 808 through these ports. The PFL tubing 916can be connected to the connection ports 809 via suitable connectionmechanisms. In one embodiment, the connection between the PFL tubing 916and the connection port 809 is a screw connection. In some embodiments,an inflation valve 810 is present in the connection port 809 and canstop the inflation media, air or liquid from escaping the inflationchannels 808 after the PFL tubing is disconnected. In some embodiments,the distal toroid 807 b and the proximal toroid 807 a may be inflatedindependently. In some embodiments, the distal toroid 807 b can beinflated separately from the struts 806 and the proximal toroid 807 a.The separate inflation is useful during the positioning of the implantat the implantation site. With reference to FIGS. 3C and 3D, in someembodiments, the portion of struts 806 that runs parallel to the toroids807 is encapsulated within the folds 801 of the implant 800. This mayalso aid in reducing the cross-sectional profile when the implant iscompressed or folded.

As mentioned above, the inflatable rings or toroids 807 and struts 806form the inflatable structure 813, which, in turn, defines the inflationchannels 808. The inflation channels 808 receive inflation media togenerally inflate the inflatable structure 813. When inflated, theinflatable rings 807 and struts 806 can provide structural support tothe inflatable implant 800 and/or help to secure the implant 800 thinthe heart 10. Uninflated, the implant 800 is a generally thin, flexibleshapeless assembly that is preferably uncapable of support and isadvantageously able to take a small, reduced profile form in which itcan be percutaneously inserted into the body. As will be explained inmore detail below, in modified embodiments, the inflatable structure 813may comprise any of a variety of configurations of inflation channels808 that can be formed from other inflatable members in addition to orin the alternative to the inflatable rings 807 and struts 806 shown inFIGS. 3A and 3B. In one embodiment, the valve has an expanded diameterthat is greater than or equal to 22 millimeters and a maximum compresseddiameter that is less than or equal to 6 millimeters (18 F).

With particular reference to FIG. 3B, in the illustrated embodiment, thedistal ring 807 b and struts 806 are joined such that the inflationchannel 808 of the distal ring 807 b is in fluid communication with theinflation channel 808 of some of the struts 806. The inflation channel808 of the proximal ring 807 a is also in communication with theinflation channels 808 of the proximal ring 807 a and a few of thestruts 806. In this manner, the inflation channels of the (i) proximalring 807 a and a few struts 806 can be inflated independently from the(ii) distal ring 807 b and some struts. In some embodiments, theinflation channel of the proximal ring 807 a is in communication withthe inflation channel of the struts 806, while the inflation channel ofthe distal ring 807 b is not in communication with the inflation channelof the struts. As will be explained in more detail below, the two groupsof inflation channels 808 are preferably connected to independent PFLtubing 916 to facilitate the independent inflation. It should beappreciated that in modified embodiments the inflatable structure caninclude less (i.e., one common inflation channel) or more independentinflation channels. For example, in one embodiment, the inflationchannels of the proximal ring 807 a, struts 806 and distal ring 807 bcan all be in fluid communication with each other such that they can beinflated from a single inflation device. In another embodiment, theinflation channels of the proximal ring 807 a, struts 806 and distalring 807 b can all be separated and therefore utilize three inflationdevices.

With reference to FIG. 3B, in the illustrated embodiment, each of theproximal ring 807 a and the distal ring 807 b has a cross-sectionaldiameter of about 0.090 inches. The struts have a cross-sectionaldiameter of about 0.060 inches. In some embodiments, within theinflation channels 808 are also housed valve systems that allow forpressurization without leakage or passage of fluid in a singledirection. In the illustrated embodiment shown in FIG. 3B, two endvalves or inflation valves 810 reside at each end section of theinflation channels 808 adjacent to the connection ports 809. These endvalves 810 are utilized to fill and exchange fluids such as saline,contrast agent and inflation media. The length of this inflation channel808 may vary depending upon the size of the implant 800 and thecomplexity of the geometry. The inflation channel material may be blownusing heat and pressure from materials such as nylon, polyethylene,Pebax, polypropylene or other common materials that will maintainpressurization. The fluids that are introduced are used to create thesupport structure, where without them, the implant 800 is an undefinedfabric and tissue assembly. In one embodiment the inflation channels 808are first filled with saline and contrast agent for radiopaquevisualization under fluoroscopy. This can make positioning the implant800 at the implantation site easier. This fluid is introduced from theproximal end of the catheter 900 with the aid of an inflation devicesuch as an endoflator or other means to pressurize fluid in a controlledmanner. This fluid is transferred from the proximal end of the catheter900 through the PFL tubes 916 which are connected to the implant 800 atthe end of each inflation channel 808 at the connection port 809.

With reference to FIG. 3B, in the illustrated embodiment, the inflationchannel 808 can have an end valve 810 (i.e., inflation valve) at eachend whereby they can be separated from the PFL tubes 916 thusdisconnecting the catheter from the implant. This connection can be ascrew or threaded connection, a colleting system, an interference fit orother means of reliable securement between the two components (i.e., theend valve 810 and the PFL tubes 916). In between the ends of theinflation channel 808 is an additional directional valve 811 to allowfluid to pass in a single direction. This allows for the filling of eachend of the inflation channel 808 and displacement of fluid in a singledirection. Once the implant 808 is placed at the desired position whileinflated with saline and contrast agent, this fluid can be displaced byan inflation media that can solidify or harden. As the inflation mediais introduced from the proximal end of the catheter 900, the fluidcontaining saline and contrast agent is pushed out from one end of theinflation channel 808. Once the inflation media completely displaces thefirst fluid, the PFL tubes are then disconnected from the implant 800while the implant 800 remains inflated and pressurized. The pressure ismaintained in the implant 800 by the integral valve (i.e., end valve810) at each end of the inflation channel 808. In the illustratedembodiment, this end valve 810 has a ball 303 and seat to allow forfluid to pass when connected and seal when disconnected. In some casethe implant 800 has three or more connection ports 809, but only twohave inflation valves 810 attached. The connection port without the endvalve 810 may use the same attachment means such as a screw or threadedelement. Since this connection port is not used for communication withthe support structure 813 and its filling, no inflation valve 810 isnecessary. In other embodiments, all three connection ports 809 may haveinflation valves 810 for introducing fluids or inflation media.

With reference to FIG. 4, the end valve system 810 comprises a tubularsection 312 with a soft seal 304 and spherical ball 303 to create asealing mechanism 313. The tubular section 312 in one embodiment isabout 0.5 cm to about 2 cm in length and has an outer diameter of about0.010 inches to about 0.090 inches with a wall thickness of about 0.005inches to about 0.040 inches. The material may include a host ofpolymers such as nylon, polyethylene, Pebax, polypropylene or othercommon materials such as stainless steel, Nitinol or other metallicmaterials used in medical devices. The soft seal material may beintroduced as a liquid silicone or other material where a curing occursthus allowing for a through hole to be constructed by coring or blankinga central lumen through the seal material. The soft seal 304 is adheredto the inner diameter of the wall of the tubular member 312 with athrough hole for fluid flow. The spherical ball 303 is allowed to movewithin the inner diameter of the tubular member 312 where it seats atone end sealing pressure within the inflation channels and is moved theother direction with the introduction of the PFL tube 916 but notallowed to migrate too far as a stop ring or ball stopper 305 retainsthe spherical ball 303 from moving into the inflation channel 808. Asthe PFL tube 916 is screwed into the connection port 809, the sphericalball 303 is moved into an open position to allow for fluid communicationbetween the inflation channel 808 and the PFL tube 916. Whendisconnected, the ball 303 is allowed to move against the soft seal 304and halt any fluid communication external to the inflation channel 808leaving the implant 800 pressurized. Additional embodiments may utilizea spring mechanism to return the ball to a sealed position and othershapes of sealing devices may be used rather than a spherical ball. Aduck-bill style sealing mechanism or flap valve would additionallysuffice to halt fluid leakage and provide a closed system to theimplant. Additional end valve systems have been described in U.S. PatentPublication No. 2009/0088836 to Bishop et al., which is therebyincorporated by reference herein.

The implant 800 allows the physician to deliver a prosthetic valve viacatheterization in a lower profile and a safer manner than currentlyavailable. When the implant 800 is delivered to the site via a deliverycatheter 900, the implant 800 is a thin, generally shapeless assembly inneed of structure and definition. At the implantation site, theinflation media (e.g., a fluid or gas) may be added via PFL tubes of thedelivery catheter 900 to the inflation channels 808 providing structureand definition to the implant 800. The inflation media thereforecomprises part of the support structure for implant 800 after it isinflated. The inflation media that is inserted into the inflationchannels 808 can be pressurized and/or can solidify in situ to providestructure to the implant 800. Additional details and embodiments of theimplant 800, can be found in U.S. Pat. No. 5,554,185 to Block and U.S.Patent Publication No. 2006/0088836 to Bishop et al., the disclosures ofwhich are expressly incorporated by reference in their entirety herein.

The cuff 802 may be made from many different materials such as Dacron,TFE, PTFE, ePTFE, woven metal fabrics, braided structures, or othergenerally accepted implantable materials. These materials may also becast, extruded, or seamed together using heat, direct or indirect,sintering techniques, laser energy sources, ultrasound techniques,molding or thermoforming technologies. Since the inflation channels 808generally surrounds the cuff 802, and the inflation channels 808 can beformed by separate members (e.g., balloons and struts), the attachmentor encapsulation of these inflation channels 808 can be in intimatecontact with the cuff material. In some embodiments, the inflationchannels 808 are encapsulated in the folds 801 or lumens made from thecuff material sewn to the cuff 802. These inflation channels 808 canalso be formed by sealing the cuff material to create an integral lumenfrom the cuff 802 itself. For example, by adding a material such as asilicone layer to a porous material such as Dacron, the fabric canresist fluid penetration or hold pressures if sealed. Materials may alsobe added to the sheet or cylinder material to create a fluid-tightbarrier.

Various shapes of the cuff 802 may be manufactured to best fitanatomical variations from person to person. As described above, thesemay include a simple cylinder, a hyperboloid, a device with a largerdiameter in its mid portion and a smaller diameter at one or both ends,a funnel type configuration or other conforming shape to nativeanatomies. The shape of the implant 800 is preferably contoured toengage a feature of the native anatomy in such a way as to prevent themigration of the device in a proximal or distal direction. In oneembodiment the feature that the device engages is the aortic root oraortic bulb 34 (see e.g., FIG. 2A), or the sinuses of the coronaryarteries. In another embodiment the feature that the device engages isthe native valve annulus, the native valve or a portion of the nativevalve. In certain embodiments, the feature that the implant 800 engagesto prevent migration has a diametral difference between 1% and 10%. Inanother embodiment, the feature that the implant 800 engages to preventmigration the diameter difference is between 5% and 40%. In certainembodiments the diameter difference is defined by the free shape of theimplant 800. In another embodiment the diameter difference preventsmigration in only one direction. In another embodiment, the diameterdifference prevents migration in two directions, for example proximaland distal or retrograde and antigrade. Similar to surgical valves, theimplant 800 will vary in diameter ranging from about 14 mm to about 30mm and have a height ranging from about 10 mm to about 30 mm in theportion of the implant 800 where the leaflets of the valve 104 aremounted. Portions of the implant 800 intended for placement in theaortic root may have larger diameters preferably ranging from about 20mm to about 45 mm. In some embodiment, the implant 800 has an outsidediameter greater than about 22 mm when fully inflated.

In certain embodiments, the cuffs, inflated structure can conform (atleast partially) to the anatomy of the patient as the implant 800 isinflated. Such an arrangement may provide a better seal between thepatient's anatomy and the implant 800.

Different diameters of prosthetic valves will be needed to replacenative valves of various sizes. For different locations in the anatomy,different lengths of prosthetic valves or anchoring devices will also berequired. For example a valve designed to replace the native aorticvalve needs to have a relatively short length because of the location ofthe coronary artery ostium (left and right arteries). A valve designedto replace or supplement a pulmonary valve could have significantlygreater length because the anatomy of the pulmonary artery allows foradditional length. Different anchoring mechanisms that may be useful foranchoring the implant 800 have been described in U.S. Patent PublicationNo. 2009/0088836 to Bishop et al.

In the embodiments described herein, the inflation channels 808 may beconfigured such that they are of round, oval, square, rectangular orparabolic shape in cross section. Round cross sections may vary fromabout 0.020-about 0.100 inches in diameter with wall thicknesses rangingfrom about 0.0005-about 0.010 inches. Oval cross sections may have anaspect ratio of two or three to one depending upon the desired cuffthickness and strength desired. In embodiments in which the inflationchannels 808 are formed by balloons, these channels 808 can beconstructed from conventional balloon materials such as nylon,polyethylene, PEEK, silicone or other generally accepted medical devicematerial

In some embodiments, portions of the cuff or body 802 can beradio-opaque to aid in visualizing the position and orientation of theimplant 800. Markers made from platinum gold or tantalum or otherappropriate materials may be used. These may be used to identifycritical areas of the valve that must be positioned appropriately, forexample the valve commissures may need to be positioned appropriatelyrelative to the coronary arteries for an aortic valve. Additionallyduring the procedure it may be advantageous to catheterize the coronaryarteries using radio-opaque tipped guide catheters so that the ostia canbe visualized. Special catheters could be developed with increasedradio-opacity or larger than standard perfusion holes. The catheterscould also have a reduced diameter in their proximal section allowingthem to be introduced with the valve deployment catheter.

As mentioned above, during delivery, the body 802 is limp and flexibleproviding a compact shape to fit inside a delivery sheath. The body 802is therefore preferably made form a thin, flexible material that isbiocompatible and may aid in tissue growth at the interface with thenative tissue. A few examples of material may be Dacron, ePTFE, PTFE,TFE, woven material such as stainless steel, platinum, MP35N, polyesteror other implantable metal or polymer. As mentioned above with referenceto FIG. 2A, the body 802 may have a tubular or hyperboloid shape toallow for the native valve to be excluded beneath the wall of the cuff802. Within this cuff 802 the inflation channels 808 can be connected toa catheter lumen for the delivery of an inflation media to define andadd structure to the implant 800. The valve 104, which is configuredsuch that a fluid, such as blood, may be allowed to flow in a singledirection or limit flow in one or both directions, is positioned withinthe cuff 802. The attachment method of the valve 104 to the cuff 802 canbe by conventional sewing, gluing, welding, interference or other meansgenerally accepted by industry.

In one embodiment, the cuff 802 would have a diameter of between about15 mm and about 30 mm and a length of between about 6 mm and about 70mm. The wall thickness would have an ideal range from about 0.01 mm toabout 2 mm. As described above, the cuff 802 may gain longitudinalsupport in situ from members formed by inflation channels or formed bypolymer or solid structural elements providing axial separation. Theinner diameter of the cuff 802 may have a fixed dimension providing aconstant size for valve attachment and a predictable valve open andclosure function. Portions of the outer surface of the cuff 802 mayoptionally be compliant and allow the implant 800 to achieveinterference fit with the native anatomy.

The implant 800 can have various overall shapes (e.g., an hourglassshape to hold the device in position around the valve annulus, or thedevice may have a different shape to hold the device in position inanother portion of the native anatomy, such as the aortic root).Regardless of the overall shape of the implant 800, the inflatablechannels 808 can be located near the proximal and distal ends 803, 804of the implant 800, preferably forming a configuration that approximatesa ring or toroid 807. These channels may be connected by intermediatechannels designed to serve any combination of three functions: (i)provide support to the tissue excluded by the implant 800, (ii) provideaxial and radial strength and stiffness to the 800, and/or (iii) toprovide support for the valve 104. The specific design characteristicsor orientation of the inflatable structure 813 can be optimized tobetter serve each function. For example if an inflatable channel 808were designed to add axial strength to the relevant section of thedevice, the channels 808 would ideally be oriented in a substantiallyaxial direction.

The cuff 802 and inflation channels 808 of the implant 800 can bemanufactured in a variety of ways. In one embodiment the cuff 802 ismanufactured from a fabric, similar to those fabrics typically used inendovascular grafts or for the cuffs of surgically implanted prostheticheart valves. The fabric is preferably woven into a tubular shape forsome portions of the cuff 802. The fabric may also be woven into sheets.In one embodiment, the yarn used to manufacture the fabric is preferablya twisted yarn, but monofilament or braided yarns may also be used. Theuseful range of yarn diameters is from approximately 0.0005 of an inchin diameter to approximately 0.005 of an inch in diameter. Depending onhow tight the weave is made. Preferably, the fabric is woven withbetween about 50 and about 500 yarns per inch. In one embodiment, afabric tube is woven with a 18 mm diameter with 200 yarns per inch orpicks per inch. Each yarn is made of 20 filaments of a PET material. Thefinal thickness of this woven fabric tube is 0.005 inches for the singlewall of the tube. Depending on the desired profile of the implant 800and the desired permeability of the fabric to blood or other fluidsdifferent weaves may be used. Any biocompatible material may be used tomake the yarn, some embodiments include nylon and PET. Other materialsor other combinations of materials are possible, including Teflon,floropolymers, polyimide, metals such as stainless steel, titanium,Nitinol, other shape memory alloys, alloys comprised primarily of acombinations of cobalt, chromium, nickel, and molybdenum. Fibers may beadded to the yarn to increases strength or radiopacity, or to deliver apharmaceutical agent. The fabric tube may also be manufactured by abraiding process.

The fabric can be stitched, sutured, sealed, melted, glued or bondedtogether to form the desired shape of the implant 800. The preferredmethod for attaching portions of the fabric together is stitching. Thepreferred embodiment uses a polypropylene monofilament suture material,with a diameter of approximately 0.005 of an inch. The suture materialmay range from about 0.001 to about 0.010 inches in diameter. Largersuture materials may be used at higher stress locations such as wherethe valve commissures attach to the cuff. The suture material may be ofany acceptable implant grade material. Preferably a biocompatible suturematerial is used such as polypropylene. Nylon and polyethylene are alsocommonly used suture materials. Other materials or other combinations ofmaterials are possible, including Teflon, fluoropolymers, polyimides,metals such as stainless steel, titanium, Kevlar, Nitinol, other shapememory alloys, alloys comprised primarily of a combinations of cobalt,chromium, nickel, and molybdenum such as MP35N. Preferably the suturesare a monofilament design. Multi strand braided or twisted suturematerials also may be used. Many suture and stitching patterns arepossible and have been described in various texts. The preferredstitching method is using some type of lock stitch, of a design suchthat if the suture breaks in a portion of its length the entire runninglength of the suture will resist unraveling. And the suture will stillgenerally perform its function of holding the layers of fabric together.

In some embodiments, the implant 800 is not provided with separateballoons, instead the fabric of the cuff 802 itself can form theinflation channels 808. For example, in one embodiment two fabric tubesof a diameter similar to the desired final diameter of the implant 800are place coaxial to each other. The two fabric tubes are stitched,fused, glued or otherwise coupled together in a pattern of channels 808that is suitable for creating the geometry of the inflatable structure813. In some embodiments, the fabric tubes are sewn together in apattern so that the proximal and distal ends of the fabric tubes form anannular ring or toroid 807. In some embodiments, the middle section ofthe implant 800 contains one or more inflation channels shaped in astep-function pattern. In some embodiments, the fabric tubes are sewntogether at the middle section of the implant to form inflation channels808 that are perpendicular to the toroids 807 at the end sections of theimplant 800. Methods for fabricating the implant 800 have been describedin U.S. Patent Publication No. 2006/0088836 to Bishop et al.

In the illustrated embodiment of FIGS. 3A and 3B, the struts 806 arearranged such that there is no radial overlap with the distal andproximal rings 807 a, 807 b. That is, in the illustrated embodiment, thestruts 808 do not increase the radial thickness of the inflationstructure because there is no radial overlap between the distal andproximal rings and the channels so that the channels lie within theradial thickness envelop defined by the distal and proximal rings 807 a,807 b. In another embodiment, the struts 808 can be wider in the radialdirection than the distal and proximal rings 807 a, 807 b such that thedistal and proximal rings 807 a, 807 b lie within a radial thicknessenvelop defined by the struts 806.

In one embodiment, the valve 800 can be delivered through a deploymentcatheter with an 18 F or smaller outer diameter and when fully inflatedhas an effective orifice area of at least about 1.0 square cm; and inanother embodiment at least about 1.3 square cm and in anotherembodiment about 1.5 square cm. In one embodiment, the valve 800 has aminimum cross-sectional flow area of at least about 1.75 square cm.

Leaflet Subassembly

With reference back to the embodiments of FIG. 2A, the valve 104preferably is a tissue-type heart valve that includes a dimensionallystable, pre-aligned tissue leaflet subassembly. Pursuant to thisconstruction, an exemplary tissue valve 104 includes a plurality oftissue leaflets that are templated and attached together at their tipsto form a dimensionally stable and dimensionally consistent coaptingleaflet subassembly. Then, in what can be a single process, each of theleaflets of the subassembly is aligned with and individually sewn to thecuff 802, from the tip of one commissure uniformly, around the leafletcusp perimeter, to the tip of an adjacent commissure. As a result, thesewed sutures act like similarly aligned staples, all of which equallytake the loading force acting along the entire cusp of each of thepre-aligned, coapting leaflets. Once inflated, the cuff 802 supports thecommissures with the inflation media and its respective pressure whichwill solidify and create a system similar to a stent structure. Theresulting implant 800 thereby formed can reduce stress and potentialfatigue at the leaflet suture interface by distributing stress evenlyover the entire leaflet cusp from commissure to commissure. In someembodiments, the tissue valve is coupled to the inflatable cuff 802 byattaching to the fabric of the cuff only.

In one embodiment, the tissue leaflets are not coupled to each other butare instead individually attached to the cuff 802.

A number of additional advantages result from the use of the implant 800and the cuff 802 construction utilized therein. For example, for eachkey area of the cuff 802, the flexibility can be optimized orcustomized. If desired, the coapting tissue leaflet commissures can bemade more or less flexible to allow for more or less deflection torelieve stresses on the tissue at closing or to fine tune the operationof the valve. Similarly, the base radial stiffness of the overallimplant structure can be increased or decreased by pressure or inflationmedia to preserve the roundness and shape of the implant 800.

Attachment of the valve 104 to the cuff 802 can be completed in anynumber of conventional methods including sewing, ring or sleeveattachments, gluing, welding, interference fits, bonding throughmechanical means such as pinching between members. An example of thesemethods are described in Published Applications from Huynh et al (Ser.No. 06/102,944) or Lafrance et al (2003/0027332) or U.S. Pat. No.6,409,759 to Peredo, which are hereby incorporated by reference herein.These methods are generally know and accepted in the valve deviceindustry. The valve, whether it is tissue, engineered tissue, mechanicalor polymer, may be attached before packaging or in the hospital justbefore implantation. Some tissue valves are native valves such as pig,horse, cow or native human valves. Most of which are suspended in afixing solution such as Glutaraldehyde.

In some embodiments, heart valve prostheses can be constructed withflexible tissue leaflets or polymer leaflets. Prosthetic tissue heartvalves can be derived from, for example, porcine heart valves ormanufactured from other biological material, such as bovine or equinepericardium. Biological materials in prosthetic heart valves generallyhave profile and surface characteristics that provide laminar,nonturbulent blood flow. Therefore, intravascular clotting is lesslikely to occur than with mechanical heart valve prostheses.

Natural tissue valves can be derived from an animal species, typicallymammalian, such as human, bovine, porcine canine, seal or kangaroo.These tissues can be obtained from, for example, heart valves, aorticroots, aortic walls, aortic leaflets, pericardial tissue such aspericardial patches, bypass grafts, blood vessels, human umbilicaltissue and the like. These natural tissues are typically soft tissues,and generally include collagen containing material. The tissue can beliving tissue, decellularized tissue or recellularized tissue. Tissuecan be fixed by crosslinking. Fixation provides mechanicalstabilization, for example by preventing enzymatic degradation of thetissue. Glutaraldehyde or formaldehyde is typically used for fixation,but other fixatives can be used, such as other difunctional aldehydes,epoxides, genipin and derivatives thereof. Tissue can be used in eithercrosslinked or uncrosslinked form, depending on the type of tissue, useand other factors. Generally, if xenograft tissue is used, the tissue iscrosslinked and/or decellularized. Additional description of tissuevalves can be found in U.S. Patent Publication No. 2009/008836 to Bishopet al.

Inflation Media

The inflatable structure 813 can be inflated using any of a variety ofinflation media, depending upon the desired performance. In general, theinflation media can include a liquid such water or an aqueous basedsolution, a gas such as CO₂, or a hardenable media which may beintroduced into the inflation channels 808 at a first, relatively lowviscosity and converted to a second, relatively high viscosity.Viscosity enhancement may be accomplished through any of a variety ofknown UV initiated or catalyst initiated polymerization reactions, orother chemical systems known in the art. The end point of the viscosityenhancing process may result in a hardness anywhere from a gel to arigid structure, depending upon the desired performance and durability.

Useful inflation media generally include those formed by the mixing ofmultiple components and that have a cure time ranging from a tens ofminutes to about one hour, preferably from about twenty minutes to aboutone hour. Such a material may be biocompatible, exhibit long-termstability (preferably on the order of at least ten years in vivo), poseas little an embolic risk as possible, and exhibit adequate mechanicalproperties, both pre and post-cure, suitable for service in the cuff ofthe present invention in vivo. For instance, such a material should havea relatively low viscosity before solidification or curing to facilitatethe cuff and channel fill process. A desirable post-cure elastic modulusof such an inflation medium is from about 50 to about 400 psi—balancingthe need for the filled body to form an adequate seal in vivo whilemaintaining clinically relevant kink resistance of the cuff. Theinflation media ideally should be radiopaque, both acute and chronic,although this is not absolutely necessary.

One preferred family of hardenable inflation media are two part epoxies.The first part is an epoxy resin blend comprising a first aromaticdiepoxy compound and a second aliphatic diepoxy compound. The firstaromatic diepoxy compound provides good mechanical and chemicalstability in an aqueous environment while being soluble in aqueoussolution when combined with suitable aliphatic epoxies. In someembodiments, the first aromatic diepoxy compound comprises at least oneN,N-diglycidylaniline group or segment. In some embodiments, the firstaromatic diepoxy compound are optionally substitutedN,N-diglycidylaniline. The substitutent may be glycidyloxy orN,N-diglycidylanilinyl-methyl. Non-limiting examples of the firstaromatic diepoxy compound are N,N-diglycidylaniline,N,N-diclycidyl-4-glycidyloxyaniline (DGO) and4,4′-methylene-bis(N,N-diglycidylaniline) (MBD), etc.

The second aliphatic diepoxy compound provides low viscosity and goodsolubility in an aqueous solution. In some embodiments, the secondaliphatic diepoxy compound may be 1,3-butadiene diepoxide, glycidylether or C₁₋₅ alkane diols of glycidyl ether. Non-limiting examples ofthe second aliphatic diepoxy compounds are 1,3-butadiene diepoxide,butanediol diglycidyl ether (BDGE), 1,2-ethanediol diglycidyl ether,glycidyl ether, etc.

In some embodiments, additional third compound may be added to the firstpart epoxy resin blend for improving mechanical properties and chemicalresistance. In some embodiments, the additional third compound may be anaromatic epoxy other than the one containing N,N-diglycidylanaline.However, the solubility of the epoxy resin blend can also decrease andthe viscosity can increase as the concentration of the additionalaromatic epoxies increases. The preferred third compound may betris(4-hydroxyphenyl)methane triglycidyl ether (THTGE), bisphenol Adiglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), orresorcinol diglycidyl ether (RDGE).

In some embodiments, the additional third compound may be acycloaliphatic epoxy compound, preferably more soluble than the firstaromatic diepoxy compound. It can increase the mechanical properties andchemical resistance to a lesser extent than the aromatic epoxy describedabove, but it will not decrease the solubility as much. Non-limitingexamples of such cycloaliphatic epoxy are 1,4-cyclohexanedimethanoldiclycidyl ether and cyclohexene oxide diglycidyl1,2-cyclohexanedicarboxylate. Similarly, in some embodiments, aliphaticepoxy with 3 or more glycidyl ether groups, such as polyglycidyl ether,may be added as the additional third compound for the same reason.Polyglycidyl ether may increase cross linking and thus enhance themechanical properties.

In general, the solubility of the epoxy resin blend decreases and theviscosity increases as the concentration of the first aromatic diepoxycompound increases. In addition, the mechanical properties and chemicalresistance may be reduced as the concentration of the aliphatic diepoxycompound goes up in the epoxy resin blend. By adjusting the ratio of thefirst aromatic dipoxy compound and the second aliphatic diepoxycompound, a person skilled in the art can control the desired propertiesof the epoxy resin blend and the hardened media. Adding the thirdcompound in some embodiments may allow further tailoring of the epoxyresin properties.

The second part of the hardenable inflation media comprises a hardenercomprising at least one cycloaliphatic amine. It provides goodcombination of reactivity, mechanical properties and chemicalresistance. The cycloaliphatic amine may include, but not limited to,isophorone diamine (IPDA), 1,3-bisaminocyclohexame (1,3-BAC), diaminocyclohexane (DACH), n-aminoethylpiperazine (AEP) orn-aminopropylpiperazine (APP).

In some embodiments, an aliphatic amine may be added into the secondpart to increase reaction rate, but may decrease mechanical propertiesand chemical resistance. The preferred aliphatic amine has thestructural formula (I):

wherein each R is independently selected from branched or linear chainsof C₂₋₅ alkyl, preferably C₂ alkyl. The term “alkyl” as used hereinrefers to a radical of a fully saturated hydrocarbon, including, but notlimited to, methyl, ethyl, n-propyl, isopropyl (or i-propyl), n-butyl,isobutyl, tert-butyl (or t-butyl), n-hexyl, and the like. For example,the term “alkyl” as used herein includes radicals of fully saturatedhydrocarbons defined by the following general formula C_(n)H_(2n+2). Insome embodiments, the aliphatic amine may include, but not limited to,tetraehtylenepentamine (TEPA), diethylene triamine and triethylenetetraamine. In some embodiments, the hardener may further comprise atleast one radio-opaque compound, such as iodo benzoic acids.

Additional details of hardenable inflation media are described inco-pending application titled “Inflation Media Formulation,” herebyincorporated herein by reference. Other suitable inflation media arealso described in U.S. patent application Ser. No. 09/496,231 to Hubbellet al., filed Feb. 1, 2000, entitled “Biomaterials Formed byNucleophilic Addition Reaction to Conjugated Unsaturated Groups” andU.S. Pat. No. 6,958,212 to Hubbell et al. The entireties of each ofthese patents are hereby incorporated herein by reference.

Below is Listed One Particular Two-Component Medium. This MediumComprises: First Part—Epoxy Resin Blend

(1) N,N-Diglycidyl-4-glycidyloxyaniline (DGO), present in a proportionranging from about 10 to about 70 weight percent; specifically in aproportion of about 50 weight percent,

(2) Butanediol diglycidyl ether (BDGE) present in a proportion rangingfrom about 30 to about 75 weight percent; specifically in a proportionof about 50 weight percent, and optionally

(3) 1,4-Cyclohexanedimethanol diglycidyl ether, present in a proportionranging from about 0 to about 50 weight percent.

Second Part—Amine Hardener

(1) Isophorone diamine (IPDA), present in a proportion ranging fromabout 75 to about 100 weight percent, and optionally

(2) Diethylene triamine (DETA), present in a proportion ranging fromabout 0 to about 25 weight percent.

The mixed uncured inflation media preferably has a viscosity less than2000 cps. In one embodiment the epoxy based inflation media has aviscosity of 100-200 cps. In another embodiment the inflation media hasa viscosity less than 1000 cps. In some embodiments, the epoxy mixturehas an initial viscosity of less than about 50 cps, or less than about30 cps after mixing. In some embodiments, the average viscosity duringthe first 10 minutes following mixing the two components of theinflation media is about 50 cps to about 60 cps. The low viscosityensures that the inflation media can be delivered through the inflationlumen of a deployment catheter with small diameter, such as an 18 Frenchcatheter

In some embodiments, the balloon or inflation channel may be connectedto the catheter on both ends. This allows the balloon to be pre-inflatedwith a non-solidifying material such as a gas or liquid. If a gas ischosen, CO₂ or helium are the likely choices; these gasses are used toinflate intraortic balloon pumps. Preferably the pre-inflation media isradio-opaque so that the balloon position can be determined byangiography. Contrast media typically used in interventional cardiologycould be used to add sufficient radio-opacity to most liquidpre-inflation media. When it is desired to make the implant permanentand exchange the pre-inflation media for the permanent inflation media,the permanent inflation media is injected into the inflation channelthrough a first catheter connection. In some embodiments, the permanentinflation media is capable of solidifying into a semi-solid, gel orsolid state. As the permanent inflation media is introduced into theinflatable structure, the pre-inflation media is expelled out from asecond catheter connection. The catheter connections are positioned insuch a way that substantially all of the pre-inflation media is expelledas the permanent inflation media is introduced. In one embodiment anintermediate inflation media is used to prevent entrapment ofpre-inflation media in the permanent inflation media. In one embodimentthe intermediate inflation media is a gas and the pre-inflation media isa liquid. In another embodiment the intermediate inflation media orpre-inflation media functions as a primer to aid the permanent inflationmedia to bond to the inner surface of the inflation channel. In anotherembodiment the pre-inflation media or the intermediate inflation mediaserves as a release agent to prevent the permanent inflation media frombonding to the inner surface of the inflation channel.

The permanent inflation media may have a different radiopacity than thepreinflation media. A device that is excessively radiopaque tends toobscure other nearby features under angiography. During the preinflationstep it may be desirable to visualize the inflation channel clearly, soa very radiopaque inflation media may be chosen. After the device isinflated with the permanent inflation media a less radiopaque inflationmedia may be preferred. The feature of lesser radiopacity is beneficialfor visualization of proper valve function as contrast media is injectedinto the ventricle or the aorta.

Another embodiment of the inflation media is disclosed in co-pendingapplication filed on the same day as this application under AttorneyDocket: DFMED.034A, entitled INFLATION MEDIA FOR IMPLANTS, and U.S.Provisional Patent Application No. 61/346,419 filed May 19, 2011, theentirety of these applications are hereby incorporated by referenceherein.

Low Crossing Profile Delivery System

FIGS. 5A-5B illustrate an exemplary embodiment of a low crossing profiledelivery catheter 900 that can be used to deliver the implant 800. Ingeneral, the delivery system comprises a delivery catheter 900, and thedelivery catheter 900 comprises an elongate, flexible catheter bodyhaving a proximal end and a distal end. In some embodiments, thecatheter body has an outer diameter of about 18 French or lessparticularly at the distal portion of the catheter body (i.e. thedeployment portion). In some embodiments, the delivery catheter alsocomprises a cardiovascular prosthetic implant 800 at the distal end ofthe catheter body. As described herein, certain features of the implant800 and delivery catheter 900 are particularly advantageous forfacilitating delivering of cardiovascular prosthetic implant 800 anwithin a catheter body having outer diameter of about 18 French or lesswhile still maintaining a tissue valve thickness equal to or greaterthan about 0.011 inches and/or having an effective orifice area equal toor greater than about 1 cm squared, or in another embodiment, 1.3 cmsquared or in another embodiment 1.5 cm squared. In such embodiments,the implant 800 may also have an expanded maximum diameter that isgreater than or equal to about 22 mm. In some embodiments, at least onelink exists between the catheter body and the implant 800. In someembodiments, the at least one link is the PFL tubing. In one embodiment,the delivery system is compatible with 0.035″ or 0.038″ guidewire.

In general, the delivery catheter 900 can be constructed with extrudedtubing using well known techniques in the industry. In some embodiments,the catheter 900 can incorporates braided or coiled wires and or ribbonsinto the tubing for providing stiffness and rotational torqueability.Stiffening wires may number between 1 and 64. In some embodiments, abraided configuration is used that comprises between 8 and 32 wires orribbon. If wires are used in other embodiments, the diameter can rangefrom about 0.0005 inches to about 0.0070 inches. If a ribbon is used,the thickness is preferably less than the width, and ribbon thicknessesmay range from about 0.0005 inches to about 0.0070 inches while thewidths may range from about 0.0010 inches to about 0.0100 inches. Inanother embodiment, a coil is used as a stiffening member. The coil cancomprise between 1 and 8 wires or ribbons that are wrapped around thecircumference of the tube and embedded into the tube. The wires may bewound so that they are parallel to one another and in the curved planeof the surface of the tube, or multiple wires may be wrapped in opposingdirections in separate layers. The dimensions of the wires or ribbonsused for a coil can be similar to the dimensions used for a braid.

With reference to FIGS. 5A and 5B, the catheter 900 comprises an outertubular member 801 having a proximal end 902 and a distal end 903, andan inner tubular member 904 also having a proximal end 905 and a distalend 906. The inner tubular member 904 extends generally through theouter tubular member 901, such that the proximal and distal ends 902,903 of the inner tubular member 904 extend generally past the proximalend 902 and distal end 903 of the outer tubular member 901. The distalend 903 of the outer tubular member 901 comprises a sheath jacket 912.In some embodiments, the sheath jacket 912 may comprise KYNAR tubing.The sheath jacket 912 can house the implant 800 in a retracted state fordelivery to the implantation site. In some embodiments, the sheathjacket 912 is capable of transmitting at least a portion of light in thevisible spectrum. This allows the orientation of the implant 800 to bevisualized within the catheter 900. In some embodiments, an outer sheathmarking band 913 may be located at the distal end 903 of the outertubular member 901. The proximal end 905 of the inner tubular member 904is connected to a handle 907 for grasping and moving the inner tubularmember 904 with respect to the outer tubular member 901. The proximalend 902 of the outer tubular member 901 is connected to an outer sheathhandle 908 for grasping and holding the outer tubular member 901stationary with respect to the inner tubular member 904. A hemostasisseal 909 is preferably provided between the inner and outer tubularmembers 901, 904, and the hemostasis seal 909 is disposed in outersheath handle 908. In some embodiments, the outer sheath handle 908comprises a sideport valve 921, and the fluid can be passed into theouter tubular member through it.

In general, the inner tubular member 904 comprises a multilumen hypotube(see FIG. 6). In some embodiments, a neck section 910 is located at theproximal end 905 of the inner tubular member 904. The neck section 910may be made from stainless steel, Nitinol or another suitable materialwhich can serve to provide additional strength for moving the innertubular member 904 within the outer tubular member 901. In someembodiments, a mulilumen marker band 911 is present at the distal end906 of the inner tubular member 904. The multilumen hypotube has a wallthickness between about 0.004 in and about 0.006 in. In a preferredembodiment, the wall thickness is about 0.0055 in, which providessufficient column strength and increases the bending load required tokink the hypotube. With reference to FIG. 6, the inner tubular member904 (i.e., multilumen hypotube) comprises at least four lumens. One ofthe lumens accommodates the guidewire tubing 914, and each of the otherlumens accommodates a positioning-and-fill lumen (PFL) tubing 916. Theguidewire tubing 914 is configured to receive a guidewire. The PFLtubing 916 is configured to function both as a control wire forpositioning the implant 800 at the implantation cite, and as aninflation tube for delivering a liquid, gas or inflation media to theimplant 800. In particular, the tubing 916 can allow angular adjustmentof the implant 800. That is, the plane of the valve (defined generallyperpendicular to the longitudinal axis of the implant 800) can beadjusted with the tubing 916.

With reference to FIGS. 5A and 5B, in general, the guidewire tubing 914is longer than and extends throughout the length of the deliverycatheter 900. The proximal end of the guidewire tubing 914 passesthrough the inner sheath handle 907 for operator's control; the distalend of the guidewire tubing 914 extends past the distal end 903 of theouter tubular member 901, and is coupled to a guidewire tip 915. Theguidewire tip 915 can close the distal end 903 of the outer tubularmember 901 (or the receptacle) and protect the retracted implant 800,for example, during the advancement of the delivery catheter. Theguidewire tip 915 can be distanced from the outer tubular member 901 byproximally retracting the outer tubular member 901 while holding theguidewire tubing 914 stationary. Alternatively, the guidewire tubing 914can be advanced while holding the outer tubular member 901 stationary.The guidewire tubing 914 may have an inner diameter of about 0.035inches to about 0.042 inches, so the catheter system is compatible withcommon 0.035″ or 0.038″ guidewires. In some embodiments, the guidewiretubing 914 may have an inner diameter of about 0.014 inches to about0.017 inches, so the catheter system is compatible with a 0.014″diameter guidewire. The guidewire tubing 914 may be made from alubricious material such as Teflon, polypropylene or a polymerimpregnated with Teflon. It may also be coated with a lubricous orhydrophilic coating.

The guidewire tip 915 may be cone shaped, bullet shaped or hemisphericalon the front end. The largest diameter of the guidewire tip 915 ispreferably approximately the same as the distal portion 903 of the outertubular member 901. The guidewire tip 915 preferably steps down to adiameter slightly smaller than the inside diameter of the outer sheathjacket 912, so that the tip can engage the outer sheath jacket 912 andprovide a smooth transition. In the illustrated embodiment, theguidewire tip 915 is connected to the guidewire tube 914, and theguidewire lumen passes through a portion of the guidewire tip 915. Theproximal side of the guidewire tip 915 also has a cone, bullet orhemispherical shape, so that the guidewire tip 915 can easily beretraced back across the deployed implant 800, and into the deploymentcatheter 900. The guidewire tip 915 can be manufactured from a rigidpolymer such as polycarbonate, or from a lower durometer material thatallows flexibility, such as silicone. Alternatively, the guidewire tip915 may be made from multiple materials with different durometers. Forexample, the portion of the guidewire tip 915 that engages the distalportion 903 of the outer tubular member 901 can be manufactured from arigid material, while the distal and or proximal ends of the guidewiretip 915 are manufactured from a lower durmoter material.

Each PFL tubing 916 also extends throughout the length of the deliverycatheter 900. The proximal end of the PFL tubing 916 passes through thehandle 907, and has a luer lock 917 for connecting to fluid, gas orinflation media source. The distal end of the PFL tubing 916 extendspast the distal end 906 of the inner tubular member 904 through thehypotube lumen. With reference to FIG. 5C, in some embodiments, the PFLtubing 916 comprises a strain relief section 918 at the proximal endwhere the tubing 916 is connected to the luer lock 917, and the strainrelief section 918 serves to relieve the strain on the PFL tubing 916while being maneuvered by the operator. The distal end of the PFL tubing916 comprises a tip or needle 919 for connecting to the implant 800. Insome embodiments, the tip 919 may have a threaded section toward the endof the needle 919 (see FIG. 5C). In some embodiments, the PFL tubing 916may have PFL marker(s) 920 at the distal end and/or proximal end of thetubing 916 for identification.

The PFL tubing 916 is designed to accommodate for the ease of rotationin a tortuous anatomy. The tubing 916 may be constructed using polyimidebraided tube, Nitinol hypotube, or stainless steel hypotube. In apreferred embodiment, the PFL tubing 916 is made from braided polyimide,which is made of polyimide liner braided with flat wires, encapsulatedby another polyimide layer and jacketed with prebax and nylon outerlayer. In some embodiments, a Nitinol sleeve may be added to theproximal end of the PFL tubing 916 to improve torque transmission, kinksresistance and pushability. In some embodiments, the outside surface ofthe PFL tubing 916 and/or the inside surface of the lumens in themultilumen hypotube can also be coated with a lubricious siliconecoating to reduce friction. In some embodiments, an inner liningmaterial such as Teflon may be used on the inside surface of the lumensin the multilumen hypotube to reduce friction and improve performance intortuous curves. Additionally, slippery coatings such as DOW 360, MDXsilicone or a hydrophilic coating from BSI Corporation may be added toprovide another form of friction reducing elements. This can provide aprecision control of the PFL tubings 916 during positioning of theimplant 800. In some embodiments, the outside surface of the PFL tubing916 can be jacketed and reflowed with an additional nylon 12 or RelsanAESNO layer to ensure a smooth finished surface. In some embodiments,anti-thrombus coating can also be put on the outside surface of the PFLtubing 916 to reduce the risk of thrombus formation on the tubing.

In some embodiments, the outer diameter of the catheter 900 measuresgenerally about 0.030 inches to about 0.200 inches with a wall thicknessof the outer tubular member 901 being about 0.005 inches to about 0.060inches. In preferred embodiments, the outer diameter of the outertubular member 901 is between about 0.215 and about 0.219 inches. Inthis embodiment, the wall thickness of the outer tubular member 901 isbetween about 0.005 inches and about 0.030 inches. The overall length ofthe catheter 900 ranges from about 80 centimeters to about 320centimeters. In preferred embodiments, the working length of the outertubular member 901 (from the distal end of the sheath jacket 912 to thelocation where the tubular member 901 is connected to the outer sheathhandle 908) is about 100 cm to about 120 cm. In some embodiments, theinner diameter of the sheath jacket 912 is greater than or equal toabout 0.218 inches, and the outer diameter of the sheath jacket 912 isless than or equal to about 0.241 inches. In a preferred embodiment, theouter diameter of the sheath jacket portion 912 is less than or equal toabout 0.236 inches or 18 French. In some embodiments, the outer diameterof the PFL tubing 916 is less than or equal to about 0.0435 inches, andthe length is about 140 cm to about 160 cm.

In the embodiments that employ a low crossing profile outer tubularmember, a low profile inflatable implant in a retracted state ispreferable for fitting into the sheath jacket 912. The low crossingprofile outer tubular member may comprise an outer sheath with a sheathjacket 912 having an outer diameter of 18 French or less. In someembodiments, the implant 800 comprises a tissue valve 104 with anexpanded outer diameter greater than or equal to about 22 mm and atissue thickness of greater than or equal to about 0.011 inches. Thecompressed diameter of the implant 800 may be less than or equal toabout 6 mm or 18 French. The retracted implant 800 is generally loadedbetween the distal portion 903 of the outer tubular member 901 and thedistal portion 906 of the inner tubular member 904. The distal portion903 of the outer tubular member 901 therefore forms a receptacle for theimplant 800. The implant 800 may be exposed or pushed out of thereceptacle by holding the implant 800 stationary as the outer tubularmember 901 is retracted. Alternatively, the outer tubular member 901 canbe held stationary while the inner tubular member 904 is advanced andthereby pushing the implant 800 out of the receptable.

The delivery system also includes a loading tool base 925 that isconfigured to connect to the PFL tubing 916. In some embodiments, thePFL tubing 916 can connect to the loading tool base 921 via a luerconnection. With reference to FIG. 7, one end of the loading tool base921 may be configured to have step edge 923 s. In some embodiments, thedistal end of the loading tool base has three step edges 923, each stepedge 923 has a luer connector 924 for connecting the PFL tubing 916. Insome embodiments, the loading tool base 921 may also comprise at leasttwo additional connectors 922 (e.g. additional luer connectors), each influid communication with one of the luer connector 924 on the steppededges 923, which would allow the introduction of fluid, gas or air intothe implant 800 for testing purposes. For example, in the exemplifiedembodiment, once the PFL tubings 916 are connected to the loading toolbase 921, a liquid or air source can be connected to the loading toolbase 921 via the additional connectors 922. The liquid or air can thenbe introduced into the implant 800 through the loading tool base 921 andthe PFL tubings 916.

The step edges 923 on the loading tool base 921 allows the implant 800to be collapsed or folded up tightly so it can be loaded into the sheathjacket 912 at the distal end of the outer tubular member 901. When theproximal end of the PFL tubings 916 are connected to the loading toolbase 921 and the distal end connected to the connection ports 809 of theimplant 800, the step edge connections pull the PFL tubings 916 in a waythat creates an offset of the inflation valves 810 and/or the connectionports 809 in the inflation channels 808 when the implant 800 is foldedor collapsed. By staggering the connection ports/inflation valves, thecollapsed implant 800 can have a reduced cross-sectional profile. Insome embodiments, the check valve 814 in the inflation channel is alsostaggered with the connection ports/inflation valves in the collapsedstate. Accordingly, in one embodiment, the inflation valves 810 and/orthe connection ports 809 are axially aligned when the valve ispositioned within the deployment catheter in a collapsed configuration.That is, the inflation valves 810 and/or the connection ports 809 and/orcheck valve 814 are positioned such that they do not overlap with eachother but are instead aligned generally with respect to the longitudinalaxis of the deployment catheter. In this manner, the implant 800 can becollapsed into a smaller diameter as opposed to a configuration in whichwith the inflation valves 810 and/or the connection ports 809 and/orcheck valve 814 overlap each other in a radial direction, which canincrease the diameter of the compressed implant 800. In a similarmanner, the channels 806 can be arranged positioned such hat they alsodo not overlap with each other as shown in FIG. 12. As shown in FIG. 12,the loading tool base 925 can be used to pull one end of the distal andproximal rings 807 a, 807 b in a proximal direction so as to align theinflation valves 810 and/or the connection ports 809 and/or check valve814 axially as described above and/or align the channels so as to reducethe overlap between multiple channels 806.

Method of Deployment

The implant 800 may be deployed in the aortic position using the lowcrossing profile delivery system and a minimally invasive procedure. Insome embodiments, the method generally comprises gaining access to theaorta, most often through the femoral artery. The vascular access siteis prepared according to standard practice, and the guidewire isinserted into the left ventricle through the vascular access. In someembodiments, an introducer is placed in the access vessel. A balloonvalvuloplasty may optionally be performed in the case of aorticstenosis.

The catheter 900 carrying the cardiovascular prosthetic implant istranslumenally advanced to a position proximate a native valve. Afterthe delivery sheath or catheter 900 is inserted over the guidewire andadvanced over the aortic arch and past the aortic valve, the implant 800may be reveled or exposed by retracting the outer tubular member 901partially or completely while holding the inner tubular member 904stationary and allowing proper placement at or beneath the native valve.In some embodiments, the implant may also be reveled by pushing theinner tubular member 904 distally while holding the outer tubular member901 stationary. Once the implant 800 is unsheathed, it may be movedproximally or distally, and the fluid or inflation media may beintroduced to the cuff 802 providing shape and structural integrity. Insome embodiments, the distal toroid of the inflatable cuff or inflatablestructure is inflated first with a first liquid, and the implant 800 ispositioned at the implantation cite using the links between the implant800 and the catheter 900. In some embodiments, no more than three linksare present. In some embodiments, the links are PRL tubes 916, which canbe used to both control the implant 800 and to fill the inflatable cuff.

The deployment of the implant 800 can be controlled by the PFL tubes 916that are detachably coupled to the implant 800. The PFL tubes 916 areattached to the cuff 802 of the implant 800 so that the implant 800 canbe controlled and positioned after it is removed from the sheath ordelivery catheter 900. Preferably, three PFL tubes 916 are used, whichcan provide precise control of the implant 800 PFL tubes 916 duringdeployment and positioning. The PFL tubes 916 can be used to move theimplant 800 proximally and distally, or to tilt the implant 800 andchange its angle relative to the native anatomy.

In some embodiments, the implant 800 contains multiple inflation valves810 to allow the operator to inflate specific areas of the implant 800with different amounts of a first fluid or a first gas. With referenceto FIGS. 8A-C, in some embodiments, the implant 800 is initiallydeployed partially in the ventricle 32 (FIG. 8A). The inflation channel808 is filled partially, allowing the distal portion of the implant 800to open to approximately its full diameter. The implant is then pulledback into position at or near the native valve 34 annulus (FIG. 8B). Insome embodiments, the distal toroid 807 b is at least partially inflatedfirst, and the cardiovascular prosthetic implant 800 is then retractedproximally for positioning the cuff across the native valve 34. Thedistal ring 807 b seats on the ventricular side of the aortic annulus,and the implant 800 itself is placed just above the native valve 34annulus in the aortic root. At this time, the PFL tubes 916 may act tohelp separate fused commissures by the same mechanism a cutting ballooncan crack fibrous or calcified lesions. Additional inflation fluid orgas may be added to inflate the implant 800 fully, such that the implant800 extends across the native valve annulus extending slightly to eitherside (See FIG. 8C). The PFL tubes 916 provide a mechanism for forcetransmission between the handle of the deployment catheter 900 and theimplant 800. By moving all of the PFL tubes 916 together or the innertubular member 904, the implant 800 can be advanced or retracted in aproximal or distal direction. By advancing only a portion of the PFLtubes 916 relative to the other PFL tubes 916, the angle or orientationof the implant 800 can be adjusted relative to the native anatomy.Radiopaque markers on the implant 800 or on the PFL tubes 916, or theradio-opacity of the PFL tubes 916 themselves, can help to indicate theorientation of the implant 800 as the operator positions and orients theimplant 800.

In some embodiments, the implant 800 has two inflation valves 810 ateach end of the inflation channel 808 and a check valve 811 in theinflation channel 808. The check valve 811 is positioned so the fluid orgas can flow in the direction from the proximal toroid 807 a to thedistal toroid 807 b. In some embodiments, the implant 800 is fullyinflated by pressurizing the endoflator attached to the first PFL tube916 that is in communication with the first inflation valve 810 thatleads to the proximal toroid 807 a, while the endoflator attached to thesecond inflation valve 810 that is in communication with the distaltoroid 807 b is closed. The fluid or gas can flow into the distal toroid807 b through the one-way check valve. The proximal toroid 807 a is thendeflated by de-pressurizing the endoflator attached to the secondinflation valve. The distal toroid 807 b will remain inflated becausethe fluid or gas cannot escape through the check valve 811. The implant800 can then be positioned across the native annulus. Once in thesatisfactory placement, the proximal toroid 807 a can then be inflatedagain.

In some embodiments, the implant 800 may only have one inflation valve.When the inflation channel 808 is inflated with the first fluid or gas,the proximal portion of the implant 800 may be slightly restricted bythe spacing among the PFL tubes 916 while the distal portion expandsmore fully. In general, the amount that the PFL tubes 916 restricts thediameter of the proximal end of the implant 800 depends on the length ofthe PFL tubes 916 extend past the outer tubular member 901, which can beadjusted by the operator. In other embodiments, burst discs or flowrestricters are used to control the inflation of the proximal portion ofthe implant 800.

The implant 800 can also be deflated or partially deflated for furtheradjustment after the initial deployment. As shown in FIG. 9A, theimplant 800 is partially deployed and the PFL tubes 916 used to seat theimplant 800 against the native aortic valve 34. The implant 800 can thenbe fully deployed as in shown in FIG. 9B and then tested as shown inFIG. 9C. If justified by the test, the implant 800 can be deflated andmoved as shown in FIG. 9D to a more optimum position. The implant 800can then be fully deployed and released from the control wires as shownin FIG. 9E.

As discussed above, in some embodiments, the first inflation fluid orgas can be displaced by an inflation media that can harden to form amore permanent support structure in vivo. Once the operator is satisfiedwith the position of the implant 800, the PFL tubes 916 are thendisconnected, and the catheter is withdrawn leaving the implant 800behind (see FIG. 8C), along with the hardenable inflation media. Theinflation media is allowed to solidify within the inflatable cuff. Thedisconnection method may included cutting the attachments, rotatingscrews, withdrawing or shearing pins, mechanically decouplinginterlocked components, electrically separating a fuse joint, removing atrapped cylinder from a tube, fracturing a engineered zone, removing acolleting mechanism to expose a mechanical joint or many othertechniques known in the industry. In modified embodiments, these stepsmay be reversed or their order modified if desired.

The above-describe method generally describes an embodiment for thereplacement of the aortic valve. However, similar methods could be usedto replace the pulmonary valve or the mitral or tricuspid valves. Forexample, the pulmonary valve could be accessed through the venoussystem, either through the femoral vein or the jugular vein. The mitralvalve could be accessed through the venous system as described above andthen trans-septaly accessing the left atrium from the right atrium.Alternatively, the mitral valve could be accessed through the arterialsystem as described for the aortic valve, additionally the catheter canbe used to pass through the aortic valve and then back up to the mitralvalve. Additional description of mitral valve and pulmonary valvereplacement can be found in U.S. Patent Publication No. 2009/0088836 toBishop et al.

Implant Recovery

Current valve systems are often deployed through a stent-based mechanismwhere the valve is sewn to the support structure. In the inflatedembodiments described herein, the structure is added to the implantsecondarily via the inflation fluid. This allows the user to inflate orpressurize the implant 800 with any number of media including one thatwill solidify. As such, if the operator desires, the implant 800 can bemoved before the inflation media is solidified or depressurization canallow for movement of the implant within the body. Since catheter baseddevices tend to be small in diameter to reduce trauma to the vessel andallow for easier access to entry, it often difficult to remove devicessuch as stents once they have been exposed or introduced into thevasculature. However, as will be explained below, a device describedherein enables a percutaneous prosthetic aortic valve to be recoveredfrom the body and reintroduced retrograde to the introducer.

With reference to FIGS. 10A-C, the deployment control device alsoprovides a method for retracting the implant 800 back into theintroducer if the result is not satisfactory, or if the sizing of theimplant could be optimized. Thus, after the implant 800 is fully orpartially deployed (FIG. 10A), in addition to providing a mechanism totransmit axial force to the implant 800, the PFL tubes 916 describedabove provide a guide or ramp to pull the implant 800 back into theintroducer as it is retracted as shown in FIGS. 10B and 10C. In someembodiments, the outer tubular member 901 is retracted out of the vesselwhile leaving the inner tubular member 904 still attached to the implant800 prior to introducing the recovery catheter 930.

To recapture an inflatable implant 800, the implant is first deflated(FIG. 10B). In some embodiment, the implant 800 may be retracted to thetip of the inner tubular member 904 by pulling the PFL tubing 916proximally, and the implant 800 and the delivery catheter 900 are thenretracted to the tip of the introducer. The inner sheath handle 907 maybe removed by unthreading the distal portion and sliding off at theproximal end of the delivery catheter 900. In some embodiments, the luerconnections 917 on the proximal end of the PFL tubing 916 may be cut offfor the removal of the inner sheath handle 907. Optionally a pushingtube can be loaded over the guidewire and PFL tubing until adjacent tothe proximal end of the inner tubular member 904. The outer tubularmember 901 can then be removed from the delivery catheter system, whilekeeping the implant 800 stationary.

The recovery catheter 930 can then be advanced over the guidewire andthe inner tubular member 904. Once the recovery catheter 930 isproximate to the implant, the recovery sheath 931 is retracted to exposethe basket section 933. The implant 800 can then be retracted into thebasket section 933 (FIG. 10C). Once the implant 800 is completely insidethe basket section 933, in some embodiments, the PFL tubes 916 areadjusted to offset the end valves 810 in the implant 800 to allow morecompact fold. The recovery system 930 is then slowly pulled back throughthe introducer and out of the patient.

FIG. 11 illustrates one embodiment of a recovery catheter 930 forrecapturing an implant 800. As shown, the recovery catheter 930comprises an outer recovery sheath 931. The outer recovery sheath 931 isinserted over the inner shaft 932. The inner shaft 932 comprises abasket structure 933, which is coupled to the distal end of the innershaft 932 and is configured to capture the implant into the outerrecovery sheath 931 without harm to the patient. Relative movement ofthe inner shaft 932 with respect to the outer recovery sheath 931 wouldexpose the basket 933 when introduced into the body. By pulling theimplant 800 into the basket section 933 it may be safely reintroducedinto the introducer or outer recovery sheath 931. The basket 933 allowsthe implant to be guided into an introducer without harm or worry of theimplant being tethered or compiled to a larger diameter where it may notfit into the inner diameter of a sheath.

The outer recovery sheath 931 is attached to the outer recovery handleor hub 935 at the proximal end, while the inner shaft 932 is attached tothe inner recovery handle or hub 934 at the proximal end. A hemostasisvalve (not shown) is preferably disposed in each of the inner and outerrecovery handles 934 and 935. Also on the inner recovery handle 934, aflush port 936 and stop-cock can be provided for fluid introduction. Inone embodiment, the inner shaft 932 would have a length of about 40 to60 centimeters and a diameter of about 2 to about 10 millimeters. In apreferred embodiment, the outer diameter of the inner shaft 932 is lessthan or equal to 0.207″. The basket section 933 may be constructed withmaterials such as polymeric strands or Nitinol, stainless steel or MP35Nwire and attached by glue or thermal bonding techniques know in theindustry. This wire, strand or ribbon may have a diameter or dimensionof about 0.002 to 0.020 of an inch. The set or expanded shape would beabout 1.00 to 1.50 inches and the length of the basket section 933 wouldmeasure about 6 to 9 inches in length. In another embodiment, the basketsection 933 is made out of a fabric, where the fabric basket may containa feature such as a preshaped wire or a balloon to facilitate itsopening.

The basket section 933 can be formed by heat setting or other mannersinto a cone shape with a free diameter slightly larger than the patientsaorta. In another embodiment, the braided basket is manufactured fromloops of wire so that the cut ends of the wire are all located at theproximal end of the basket. The wires used to manufacture the basket 933preferably have a diameter from 0.002 in to 0.020 in. The wires may alsobe replaced by ribbons having a thickness between 0.002 in and 0.020 inand a width between 0.003 in and 0.030 in. The diameter of the small endof the basket is preferably between 0.007 in and 0.3 in the basket ispreferably be capable of collapsing to a diameter small enough to passthrough the desired introducer size. The large end of the basket sectionpreferably expands to a diameter similar to or slightly larger than thetypical human aorta, or 0.75 in to 1.50 in.

The various methods and techniques described above provide a number ofways to carry out the invention. Of course, it is to be understood thatnot necessarily all objectives or advantages described may be achievedin accordance with any particular embodiment described herein. Thus, forexample, those skilled in the art will recognize that the methods may beperformed in a manner that achieves or optimizes one advantage or groupof advantages as taught herein without necessarily achieving otherobjectives or advantages as may be taught or suggested herein.

Furthermore, the skilled artisan will recognize the interchangeabilityof various features from different embodiments disclosed herein.Similarly, the various features and steps discussed above, as well asother known equivalents for each such feature or step, can be mixed andmatched by one of ordinary skill in this art to perform methods inaccordance with principles described herein. Additionally, the methodswhich is described and illustrated herein is not limited to the exactsequence of acts described, nor is it necessarily limited to thepractice of all of the acts set forth. Other sequences of events oracts, or less than all of the events, or simultaneous occurrence of theevents, may be utilized in practicing the embodiments of the invention.

Although the invention has been disclosed in the context of certainembodiments and examples, it will be understood by those skilled in theart that the invention extends beyond the specifically disclosedembodiments to other alternative embodiments and/or uses and obviousmodifications and equivalents thereof. Accordingly, the invention is notintended to be limited by the specific disclosures of preferredembodiments herein

1.-22. (canceled)
 23. A delivery catheter for deploying a cardiovascularprosthetic implant using a minimally invasive procedure, wherein thedelivery catheter comprises: an elongate, flexible catheter body havinga proximal end and a distal end; a cardiovascular prosthetic implant atthe distal end of the catheter body, wherein the cardiovascularprosthetic implant comprises an inflatable cuff and a tissue valve, theinflatable cuff comprising inflation channels, the inflation channelsincluding at least an inflation valve, a connection port, and a checkvalve, and wherein the cardiovascular prosthetic implant is positionedwithin the distal end of the catheter body such that the inflationvalve, the connection port, and the check valve are aligned with respectto a longitudinal axis of the catheter body and do not overlap with eachother; and at least one link between the catheter body and thecardiovascular prosthetic implant.